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Disulfide cross‐links in the interaction of a cataract‐linked αA‐crystallin mutant with βB1‐crystallin
Author(s) -
Satish Kumar M.,
Koteiche Hanane A.,
Claxton Derek P.,
Mchaourab Hassane S.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.047
Subject(s) - crystallin , cysteine , chemistry , disulfide linkage , covalent bond , disulfide bond , mutant , protein subunit , arginine , protein disulfide isomerase , stereochemistry , biochemistry , amino acid , enzyme , organic chemistry , gene
A number of αA‐crystallin mutants are associated with hereditary cataract including cysteine substitution at arginine 49. We report the formation of affinity‐driven disulfide bonds in the interaction of αA‐R49C with βB1‐crystallin. To mimic cysteine thiolation in the lens, βB1‐crystallin was modified by a bimane probe through a disulfide linkage. Our data suggest a mechanism whereby a transient disulfide bond occurs between αA‐ and βB1‐crystallin followed by a disulfide exchange with cysteine 49 of a neighboring αA‐crystallin subunit. This is the first investigation of disulfide bonds in the confine of the chaperone/substrate complex where reaction rates are favored by orders of magnitude. Covalent protein cross‐links are a hallmark of age‐related cataract and may be a factor in its inherited form.